Patterns of MRI atrophy in tau positive and ubiquitin positive frontotemporal lobar degeneration

Memory and Aging Center, and Department of Neurology, University of California, San Francisco, San Francisco, California 94117, USA.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 01/2008; 78(12):1375-8. DOI: 10.1136/jnnp.2006.114231
Source: PubMed


We applied optimised voxel based morphometry (VBM) to brain MRIs from autopsy proven cases of tau positive frontotemporal lobar degeneration (FTLD-T, n = 6), ubiquitin and TDP-43 positive/tau negative FTLD (FTLD-U, n = 8) and cognitively normal controls (n = 61). The analysis revealed that FTLD-T and FTLD-U both show atrophy in the frontal cortex and striatum, but striatal atrophy is more severe in FTLD-T. Manual region of interest tracing of caudate and putamen volumes confirmed the VBM findings. These anatomical differences may help distinguish between FTLD spectrum pathological subtypes in vivo.

9 Reads
  • Source
    • "Unlike the symmetric pattern of frontotemporal brain atrophy of patients with FTDP-17T/ MAPT, patients with FTDP-17U/PGRN show asymmetric frontotemporal and parietal atrophy (Rohrer et al. 2010; Kelley et al. 2009). Caudate atrophy tends to be more common in patients with FTDP-17T/MAPT (Kim et al. 2007) and ALS-FTD/FUS compared to other genetic FTLDs (Josephs et al. 2010). Currently, mutation type and pathology trump clinical phenotypes in predicting the topographical distribution of atrophy (Whitwell et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Frontotemporal dementia is commonly associated with parkinsonism in several sporadic (i.e., progressive supranuclear palsy, corticobasal degeneration) and familial neurodegenerative disorders (i.e., frontotemporal dementia associated with parkinsonism and MAPT or progranulin mutations in chromosome 17). The clinical diagnosis of these disorders may be challenging in view of overlapping clinical features, particularly in speech, language, and behavior. The motor and cognitive phenotypes can be viewed within a spectrum of clinical, pathologic, and genetic disorders with no discrete clinicopathologic correlations but rather lying within a dementia-parkinsonism continuum. Neuroimaging and cerebrospinal fluid analysis can be helpful, but the poor specificity of clinical and imaging features has enormously challenged the development of biological markers that could differentiate these disorders premortem. This gap is critical to bridge in order to allow testing of novel biological therapies that may slow the progression of these proteinopathies.
    Journal of Molecular Neuroscience 09/2011; 45(3):343-9. DOI:10.1007/s12031-011-9632-1 · 2.34 Impact Factor
  • Source
    • "atrophy in frontal lobar regions, anterior cingulate gyri, and the insula.(Rabinovici et al., 2007) When cases of FTLD-TDP and FTLD-Tau – both clinically characterized by prominent behavior symptoms – were directly compared in two separate studies, no significant pattern of atrophy was sufficient to differentiate between the two pathologic groups.(Kim et al., 2007; Whitwell et al., 2004) However, when each specific pathologic diagnosis was examined individually, certain patterns were identified: atrophy in the bilateral orbitofrontal cortices, posterior superior temporal lobes, and posterior fusiform gyri in FTLD-TDP; bilateral dorsolateral prefrontal atrophy in Pick's disease with Pick bodies; r"
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuronal and glial changes associated with tau, TAR DNA binding protein of ∼43 kDa (TDP-43), and fused in sarcoma (FUS) together constitute the pathologic spectrum of frontotemporal lobar degeneration (FTLD). Most patients with FTLD present with prominent behavior or language changes, sometimes accompanied by extrapyramidal symptoms or motor neuron disease. Identification of FTLD patients with mutations in genes for tau, TDP-43, and FUS lends strong support for their pathogenic roles in FTLD, and elucidation of their dysfunction will pave the way for development of substrate specific therapy. However, there remains no reliable biomarker for early detection of FTLD or prediction of underlying FTLD pathologic change. Clinical syndromes usually reflects the earliest affected brain regions where atrophy can be visualized on structural MRI, but neither clinical nor structural imaging-based biomarkers has been accurately correlated with underlying pathology on the individual patient level. Biochemical markers in the cerebrospinal fluid (CSF) have also been investigated in FTLD and related disorders, including amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP). However, their accuracy and pathologic significance need to be confirmed in future multi-center studies. Here we review the progress made in FTLD biomarkers, including clinical phenotype/feature characterization, neuropsychological analysis, CSF and plasma analytes, and patterns of brain atrophy and network dysfunction detectable on brain imaging. Given the pathologic overlap of FTLD with ALS and PSP, collaboration with specialists in those fields will be essential in the translation of promising FTLD biomarkers into clinical practice.
    Progress in Neurobiology 04/2011; 95(4):636-48. DOI:10.1016/j.pneurobio.2011.04.012 · 9.99 Impact Factor
  • Source
    • "Each PPA syndrome is associated with a specific pattern of atrophy on neuroimaging but appears to have less robust relationship with underlying neuropathology[71] in contrast to a few reports that FTD-U correlates with right temporal lobe atrophy[72] or FTD-T with striatal atrophy.[73] The heterogeneity of pathological picture is possibly the result of different methodology applied to patient population with variability in the use of language tests and variations in the definitions of semantic dementia, fluency, and agrammatism. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary progressive aphasia (PPA) is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca's area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face) meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick's disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon) increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.
    Annals of Indian Academy of Neurology 12/2010; 13(Suppl 2):S109-15. DOI:10.4103/0972-2327.74255 · 0.60 Impact Factor
Show more


9 Reads
Available from